Comment on 'Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size'.

A recent molecular dynamics investigation into the stability of hemoglobin concluded that the unliganded protein is only stable in the T state when a solvent box is used in the simulations that is ten times larger than what is usually employed (El Hage et al., 2018). Here, we express three main concerns about that study. In addition, we find that with an order of magnitude more statistics, the reported box size dependence is not reproducible. Overall, no significant effects on the kinetics or thermodynamics of conformational transitions were observed

Speed limits for quantum gates in multi-qubit systems

We use analytical and numerical calculations to obtain speed limits for various unitary quantum operations in multiqubit systems under typical experimental conditions. The operations that we consider include single-, two-, and three-qubit gates, as well as quantum-state transfer in a chain of qubits. We find in particular that simple methods for implementing two-qubit gates generally provide the fastest possible implementations of these gates. We also find that the three-qubit Toffoli gate time varies greatly depending on the type of interactions and the system's geometry, taking only slightly longer than a two-qubit controlled-NOT (CNOT) gate for a triangle geometry. The speed limit for quantum-state transfer across a qubit chain is set by the maximum spin-wave speed in the chain.Comment: 7 pages (two-column), 2 figures, 2 table

Predicting kinase inhibitor resistance: Physics-based and data-driven approaches.

Resistance to small molecule drugs often emerges in cancer cells, viruses, and bacteria as a result of the evolutionary pressure exerted by the therapy. Protein mutations that directly impair drug binding are frequently involved in resistance, and the ability to anticipate these mutations would be beneficial in drug development and clinical practice. Here, we evaluate the ability of three distinct computational methods to predict ligand binding affinity changes upon protein mutation for the cancer target Abl kinase. These structure-based approaches rely on first-principle statistical mechanics, mixed physics- and knowledge-based potentials, and machine learning, and were able to estimate binding affinity changes and identify resistant mutations with remarkable accuracy. We expect that these complementary approaches will enable the routine prediction of resistance-causing mutations in a variety of other target proteins

Single-channel behavior of heteromeric α1β glycine receptors: an attempt to detect a conformational change before the channel opens

The α1β heteromeric receptors are likely to be the predominant synaptic form of glycine receptors in the adult. Their activation mechanism was investigated by fitting putative mechanisms to single-channel recordings obtained at four glycine concentrations (10-1000 µM) from rat {alpha}1{beta} receptors, expressed in human embryonic kidney 293 cells. The adequacy of each mechanism, with its fitted rate constants, was assessed by comparing experimental dwell time distributions, open-shut correlations, and the concentration-open probability (Popen) curve with the predictions of the model. A good description was obtained only if the mechanism had three glycine binding sites, allowed both partially and fully liganded openings, and predicted the presence of open-shut correlations. A strong feature of the data was the appearance of an increase in binding affinity as more glycine molecules bind, before the channel opens. One interpretation of this positive binding cooperativity is that binding sites interact, each site sensing the state of ligation of the others. An alternative, and novel, explanation is that agonist binding stabilizes a higher affinity form of the receptor that is produced by a conformational change ("flip") that is separate from, and precedes, channel opening. Both the "interaction" scheme and the flip scheme describe our data well, but the latter has fewer free parameters and above all it offers a mechanism for the affinity increase. Distinguishing between the two mechanisms will be important for our understanding of the structural dynamics of activation in the nicotinic superfamily and is important for our understanding of mutations in these receptors

Hard thermal loops with a background plasma velocity

I consider the calculation of the two and three-point functions for QED at finite temperature in the presence of a background plasma velocity. The final expressions are consistent with Lorentz invariance, gauge invariance and current conservation, pointing to a straightforward generalization of the hard thermal loop formalism to this physical situation. I also give the resulting expression for the effective action and identify the various terms.Comment: 11 pages, no figure

The intra- and interrater reliability of the action research arm test: A practical test of upper extremity function in patients with stroke

Objectives: To determine the intra- and interrater reliability of the Action Research Arm (ARA) test, to assess its ability to detect a minimal clinically important difference (MCID) of 5.7 points, and to identify less reliable test items. Design: Intrarater reliability of the sum scores and of individual items was assessed by comparing (1) the ratings of the laboratory measurements of 20 patients with the ratings of the same measurements recorded on videotape by the original rater, and (2) the repeated ratings of videotaped measurements by the same rater. Interrater reliability was assessed by comparing the ratings of the videotaped measurements of 2 raters. The resulting limits of agreement were compared with the MCID. Patients: Stratified sample, based on the intake ARA score, of 20 chronic stroke patients (median age, 62yr; median time since stroke onset, 3.6yr; mean intake ARA score, 29.2). Main Outcome Measures: Spearman's rank-order correlation coefficient (Spearman's rho); intraclass correlation coefficient (ICC); mean difference and limits of agreement, based on ARA sum scores; and weighted kappa, based on individual items. Results: All intra- and interrater Spearman's rho and ICC values were higher than .98. The mean difference between ratings was highest for the interrater pair (.75; 95% confidence interval, .02-1.48), suggesting a small systematic difference between raters. Intrarater limits of agreement were -1.66 to 2.26; interrater limits of agreement were -2.35 to 3.85. Median weighted kappas exceeded .92. Conclusion: The high intra- and interrater reliability of the ARA test was confirmed, as was its ability to detect a clinically relevant difference of 5.7 points

Half-metallic ferromagnets: From band structure to many-body effects

A review of new developments in theoretical and experimental electronic structure investigations of half-metallic ferromagnets (HMF) is presented. Being semiconductors for one spin projection and metals for another ones, these substances are promising magnetic materials for applications in spintronics (i.e., spin-dependent electronics). Classification of HMF by the peculiarities of their electronic structure and chemical bonding is discussed. Effects of electron-magnon interaction in HMF and their manifestations in magnetic, spectral, thermodynamic, and transport properties are considered. Especial attention is paid to appearance of non-quasiparticle states in the energy gap, which provide an instructive example of essentially many-body features in the electronic structure. State-of-art electronic calculations for correlated $d$-systems is discussed, and results for specific HMF (Heusler alloys, zinc-blende structure compounds, CrO$_{2},$ Fe$_{3}$O$_{4}$) are reviewed.Comment: to be published in Reviews of Modern Physics, vol 80, issue

Shape-induced anisotropy in antidot arrays from self-assembled templates

Using self-assembly of polystyrene spheres, well-ordered templates have been prepared on glass and silicon substrates. Strong guiding of self-assembly is obtained on photolithographically structured silicon substrates. Magnetic antidot arrays with three-dimensional architecture have been prepared by electrodeposition in the pores of these templates. The shape anisotropy demonstrates a crucial impact on magnetization reversal processes

Observation of negative differential conductance in a reverse-biased Ni/Ge Schottky diode

We report the experimental observation of negative differential conductance in a Ni/Ge Schottky diode. With the aid of theoretical models and numerical simulation we show that, at reverse bias, electons tunnel into the high electric field of the depletion region. This scatters the electrons into the upper valley of the Ge conduction band, which has a lower mobility. The observed negative differential conductance is hence attributed to the transferred-electron effect. This shows that Schottky contacts can be used to create hot electrons for transferred-electron devices